Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

Regulation of glucose transporter-4 intervention with S. saman leaves extract in streptozotocin-induced diabetic rats

Diabetes mellitus is the leading disorder and affects more than millions of people worldwide. Nowadays, the usage of herbal drugs is said to control adiposity and hyperglycemia. The current research investigated the anti-adiposity and antidiabetic activity of S. saman leaf extract and bioactive compounds. Therefore, the results lower the sugar absorption into the blood and reveal the extract's antidiabetic properties. STZ-induced diabetic rats, Samanea saman methanolic extract show improvement in the parameters like fasting blood glucose levels, body weight, other biochemical parameters supported by the histopathological analysis, and an increase in serum levels in the experimental groups. The antioxidant plays a vital role by increasing SOD and catalase activity levels and decreasing lipid peroxidation levels. The methanolic extract protects the tissue from oxidation stress, which is responsible for the glycemic properties. According to the findings, diabetic-treated rats had overnight blood glucose levels lower and near standard biochemical markers. Histopathology of the liver, pancreas, kidneys, and adipose tissues supported the pharmacological observations.Further, we screened and documented S. saman extract used for in vitro and in vivo methods. In terms of effectiveness, the crude extracts exhibit 0.8-fold GLUT4 down-regulation. Consequently, this result contributes to clinical trials and develops antidiabetic therapy as a substitute for synthetic pharmaceuticals.     

Effect of Genistein Intake on Some Cardiovascular Risk Factors: An Updated Systematic Review and Meta-analysis

Genistein, an isoflavone in soybean products has potential cardio-protective effects and is used also as an alternative for estrogen therapy in postmenopausal women. However, results in this regard are inconsistent and also, not all risk factors related to cardiovascular supportive effects have been meta-analyzed. We searched PubMed, Scopus, ISI Web of Science, and Google Scholar from inception up to October 2020. Random-effects meta-analysis was used for data synthesis. The search included studies with information on genistein supplementation and lipid profile [triglycerides (TG), total cholesterol (TC),low-density lipoprotein (LDL-C), and high-density lipoprotein HDL-C)], systolic and diastolic blood pressure (SBP & DBP), body mass index [BMI] and body weight. Pooled results of studies showed that genistein intake significantly reduced TC [95%CI: -0.49(-0.80, -0.18); P=0.002)], LDL-C [95%CI: -0.60(-1.10, -0.10); P=0.018)] and SBP [95%CI: -0.52(-0.90, -0.14); P=0.007)]. DBP, HLD-C, TG, BMI, and body weight showed no meaningful improvement. Subgroup analysis showed that LDL-C and SBP were reduced more effectively in postmenopausal women with metabolic syndrome. Genistein intake more than 6 months showed a greater effect on lowering cholesterol -0.76(-1.27, -0.24), SBP [-0.39(-0.70, -0.08)] and DBP -0.40(-0.81, -0.00) and increasing TG and LDL-C. This meta-analysis provides consistent evidence that genistein intake reduces the CVD risk factors of TC, LDL-C, and SBP significantly.     

青少年非自杀性自伤患者父母人格特征及认知调节情绪策略

  目的  分析青少年非自杀性自伤(non-suicidal self-injury，NSSI)患者父母人格特征、认知调节情绪策略对青少年NSSI行为的影响。  方法  选取2020年1月至2021年1月到山东第一医科大学第二附属医院、泰安市中心医院、泰安市精神病医院就诊的青少年NSSI患者为病例组(60人)，在学校、社区及医院选取健康青少年为对照组(60人)，采用中国大五人格问卷简式版、认知情绪调节问卷中文版(CERQ-C)对其父母进行问卷调查，利用Logistic回归评价青少年NSSI的影响因素。  结果  对照组父母开放性、严谨性人格得分[(40.90±6.19)(48.18±6.12)]高于病例组父母[(36.88±5.02)(44.12±6.58)](t值分别为3.90，3.50，P值均＜0.05)。对照组父母面对负性事件时在接受、积极再评价、再关注计划、积极再关注、合理分析的策略得分高于病例组父母(t值分别为3.43，3.58，2.36，5.44，3.53，P值均＜0.05)。病例组父母的神经质与合理分析(r=0.31)、灾难性(r=0.37)呈正相关；开放性与积极再关注(r=0.30)、积极再评价(r=0.27)呈正相关；接受与外向性、开放性、严谨性呈负相关(r值分别为-0.29，-0.40，-0.26)；责备他人与外向性(r=-0.35)、宜人性呈负相关(r=-0.36)；外向性与积极再关注呈负相关(r=-0.32)(P值均 < 0.05)。二元Logistic回归分析结果显示，病例组父母的经济水平、受教育年限、接受、积极再评价、合理分析、神经质、开放性、严谨性与NSSI行为呈负相关(OR值分别为0.49，0.60，0.59，0.45，0.53，0.81，0.76，0.74)，自我责难、再关注计划与青少年NSSI行为呈正相关(OR值分别为1.55，2.09)(P值均＜0.05)。  结论  青少年NSSI患者父母的人格特征、面对负性事件时的情绪调节策略影响青少年NSSI行为的发生。     

SLC及其受体CCR7与Ⅰ期非小细胞肺癌淋巴结微转移的相关性

目的 探讨溶质载体蛋白（SLC）及其受体趋化因子受体7（CCR7）与I期非小细胞肺癌（NSCLC）淋巴结微转移的相关性。方法 选取2019年1月~2020年3月于我院就诊的I期NSCLC患者127例为研究对象，按照淋巴结微转移情况分为对照组92例和转移组35例，所有患者入院后均通过根治术切除病灶，通过免疫组化方式检测病灶中SLC7A11及CCR7含量，并收集患者临床资料、实验室检查资料及影像学检查资料。通过Logistic回归分析评价SLC7A11及CCR7与淋巴结微转移之间的关系。最后通过建立ROC曲线分析两者及其联合检测对NSCLC患者微淋巴结转移的预测价值。结果 两组患者SLC7A11及CCR7表达水平存在显著差异（P＜0.05）。转移组患者病灶直径、支气管受累及TLG显著高于对照组（P＜0.05）。病灶直径（OR=49.254,95%CI=11.062~507.604）是影响NSCLC淋巴结微转移的独立危险因素（P＜0.05）。SLC7A11（OR=8.622）及CCR7（OR=8.709）表达水平是影响NSCLC淋巴结微转移的独立因素（P＜0.05）。SLC7A11、CCR7及联合诊断对NSCLC淋巴结微转移具有较好的检测价值（均P＜0.05）。联合检测特异度显著高于 SLC7A11及CCR7单独检测（2=7.292，15.125；均P＜0.01）。结论 SLC家族的中SLC7A11及其受体CCR7与NSCLC患者微淋巴结转移显著相关。     

Étude de faisabilité : l’utilisation de l’imagerie médicale en éducation thérapeutique en radiothérapie

PurposeAssess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy.Materials and methodsExperimental feasibility trial of “RCT” type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software “Stone of Orthanc”.ResultsForty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 – 2.2)) vs (+ 1.4 (1.4 – 1.8)), as well as a decrease in scores related to anxiety (? 3.0 (?4.5 - (?2.0)) vs ? 1.0 (?5.0 - 0.0)) and emotional distress ((? 5.0 (? 7.5 - (? 3.5)) vs (? 2.0 (? 5.0 - (? 1.0)) A significant reduction (p = 0.043) is observed for the depression score ((? 2.0 (?3.0 - (?1.5)) vs (0.0 (0.0 – 0.0)).ConclusionThis study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted.     

李延应用泽泻汤合温胆汤治疗舒张压高的临床经验

随着社会的发展,人类生活方式的改变,高血压病越来越高发,具有低龄化趋势,代谢综合征常伴随发生,此种情况下的高血压往往是以舒张压升高为主,临床表现常与“亚健康”状态混淆,未能引起患者甚至部分医生的重视,然而事实上越来越多的科学研究证实舒张压高之危害十分明显,不容忽视。尽管现代医学对舒张压高的病因及病理机制有明确的阐述,但是暂时没有特效的药物。李延教授在治疗高血压病方面有着丰富的临床经验,临床中运用泽泻汤合温胆汤加减治疗舒张压高之眩晕,切中病机,加减灵活,屡有良效。文中从中医角度阐述舒张压高的病因病机,介绍李师辨病辨证思路,组方用药特点,附三则典型验案,另加个人心得体会,以期为舒张压高的有效治疗提供思路。